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Wiechmann, T.* ; Röh, S.* ; Sauer, S.* ; Czamara, D.* ; Arloth, J. ; Ködel, M.* ; Beintner, M.* ; Knop, L.* ; Menke, A.* ; Binder, E.B.* ; Provençal, N.*

Identification of dynamic glucocorticoid-induced methylation changes at the FKBP5 locus.

Clin. Epigenet. 11:83 (2019)
Verlagsversion DOI
Open Access Gold
Creative Commons Lizenzvertrag
BackgroundEpigenetic mechanisms may play a major role in the biological embedding of early-life stress (ELS). One proposed mechanism is that glucocorticoid (GC) release following ELS exposure induces long-lasting alterations in DNA methylation (DNAm) of important regulatory genes of the stress response. Here, we investigate the dynamics of GC-dependent methylation changes in key regulatory regions of the FKBP5 locus in which ELS-associated DNAm changes have been reported.ResultsWe repeatedly measured DNAm in human peripheral blood samples from 2 independent cohorts exposed to the GC agonist dexamethasone (DEX) using a targeted bisulfite sequencing approach, complemented by data from Illumina 450K arrays. We detected differentially methylated CpGs in enhancers co-localizing with GC receptor binding sites after acute DEX treatment (1h, 3h, 6h), which returned to baseline levels within 23h. These changes withstood correction for immune cell count differences. While we observed main effects of sex, age, body mass index, smoking, and depression symptoms on FKBP5 methylation levels, only the functional FKBP5 SNP (rs1360780) moderated the dynamic changes following DEX. This genotype effect was observed in both cohorts and included sites previously shown to be associated with ELS.ConclusionOur study highlights that DNAm levels within regulatory regions of the FKBP5 locus show dynamic changes following a GC challenge and suggest that factors influencing the dynamics of this regulation may contribute to the previously reported alterations in DNAm associated with current and past ELS exposure.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Schlagwörter Dna Methylation ; Fkbp5 ; Glucocorticoid Receptor ; Early-life Stress ; Targeted Bisulfite Sequencing ; Dexamethasone; Dna Methylation; Childhood Adversity; Life Events; Gene; Ctcf; Stress; Dexamethasone; Expression; Receptor; Binding
ISSN (print) / ISBN 1868-7075
e-ISSN 1868-7083
Zeitschrift Clinical Epigenetics
Quellenangaben Band: 11, Heft: 1, Seiten: , Artikelnummer: 83 Supplement: ,
Verlag Springer
Verlagsort Berlin : Heidelberg
Begutachtungsstatus